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Very little in known about his early life, although Jordan of Saxony claimed in his late 14th century work Liber Vitasfratrum that Giles belonged to the Colonna family of Rome. But Jordan of Saxony was not a contemporary of Giles, and many scholars remain skeptical of his account of Giles' early life. Having entered the Order of the Hermits of St. Augustine at Rome, he was sent to Paris for his philosophical and theological studies, and became there the disciple of Thomas Aquinas. He was the first Augustinian appointed to teach in the University of Paris.

It is likely that Giles was a student of Thomas Aquinas during the period between 1269 and 1272. He began many of his commentaries on the works of Aristotle during the 1270s. Giles was in Paris doing theology until Bishop Étienne Tempier condemned the Aristotelian school of thought, including those who wrote commentaries on Aristotle's work, in the Condemnation of 1277. Giles, whose work had been condemned, disappeared from the Paris academic scene. There is no information on Giles between the period of 1277 and 1281, when he returned to Italy. However, in 1281, at the Thirty-sixth Council of Paris, in which several differences between bishops and mendicant orders were arranged, he sided with the bishops against the regulars. Referring to this, a contemporary philosopher, Godfrey of Fontaines mentioned him as the most renowned theologian of the whole city (qui modo melior de totâ villâ in omnibus reputatur), suggesting he might have been in Paris during this period before going back to Rome.

Philip III of France entrusted to him the education of his son, who later, in 1285, ascended the throne as Philip IV. When the new king, after his coronation at Reims, entered Paris, Giles gave the address of welcome in the name of the university, insisting on justice as the most important virtue of a king. (For the text, see Ossinger, in work cited below.)

In 1285 Giles' work was again called into question, but by 1287 he was allowed to continue teaching. Eight years later in 1295 Giles was appointed as the archbishop of Bourges, which he wrote about in his work De renunciatione.

Giles was involved in the condemnation of 1277 promulgated by Étienne Tempier. Several of his opinions had been found reprehensible by Archbishop Tempier, and in 1285 Pope Honorius IV asked him for a public retraction. This, however, was far from lessening his reputation, for in 1287 a decree of the general chapter of the Augustinians held in Florence, after remarking that Giles's doctrine "shines throughout the whole world" (venerabilis magistri nostri Ægidii doctrina mundum universum illustrat), commanded all members of the order to accept and defend all his opinions, written or to be written.

After filling several important positions in his order he was elected superior-general in 1292. Three years later Pope Boniface VIII appointed him Archbishop of Bourges, France, although Jean de Savigny had already been designated for this see by Pope Celestine V. The French nobility protested on the ground that Colonna was an Italian, but his appointment was maintained and approved by the king.

His writings cover the fields of philosophy and theology. There is no complete edition of his works, but several treatises have been published separately.

In Holy Scripture and theology he wrote commentaries on the Hexaemeron, the Canticle of Canticles, and the Epistle to the Romans; several Opuscula and Quodlibeta, various treatises, and especially commentaries on Peter the Lombard's Four Books of Sentences.

In philosophy, besides commentaries on almost all the works of Aristotle, he wrote several special treatises. But his main work is the treatise De regimine principum, written for, and dedicated to, his pupil, Philip IV. It passed through many editions (the first, Augsburg, 1473) and was translated into several languages. The Roman edition of 1607 contains a life of Egidio. The work is divided into three books: the first treats of the individual conduct of the king, the nature of his true happiness, the choice and acquisition of virtues, and the ruling of passions; the second deals with family life and the relations with wife, children, and servants; the third considers the State, its origin, and the proper mode of governing in times of peace and war.

His pedagogical writings have been published in German by Kaufmann (Freiburg, 1904).

His attitude in the difficulties between Pope Boniface VIII and King Philip IV was long believed to have been favourable to the king. But it has been proved that he is the author of the treatise De potestate ecclesiasticâ, in which the rights of the pope are vindicated. The similarity between this treatise and the bullUnam Sanctam seems to support the view taken by some writers that he was the author of the bull.

He had already taken an active part in ending the discussions and controversies concerning the validity of Boniface's election to the papacy. In his treatise De renunciatione Papæ sive Apologia pro Bonifacio VIII he shows the legitimacy of Celestine's resignation and consequently of Boniface's election. In philosophy and theology he generally follows the opinions of his master, St. Thomas, whose works he quotes as scripta communia.

The Defensorium seu Correctorium corruptorii librorum Sancti Thomæ Acquinatis against the Franciscan William de la Mare of Oxford is by some attributed to him; but this remains uncertain. Nevertheless, on many points he holds independent views and abandons the Thomistic doctrine to follow the opinions of St. Augustine and of the Franciscan School. He even errs in asserting that, before the Fall, grace had not been given to Adam, an opinion which he wrongly attributes to St. Augustine.

For some time after this other opinions prevailed in the Augustinian Order. But as late as the seventeenth century should be mentioned Raffaello Bonherba (d. 1681) who wrote Disputationes totius philosophiæ … in quibus omnes philosophicæ inter D. Thomam et Scotum controversiæ principaliter cum doctrinâ nostri Ægidii Columnæ illustrantur (Palermo, 1645, 1671); and Augustino Arpe (d. 1704) who wrote Summa totius theologiæ Ægidii Columnæ (Bologna, 1701, and Genoa, 1704).